We have developed and are optimizing a prototype drug-eluting surgical mesh comprised of novel copolymer blends for controlled locoregional delivery of chemotherapy to prevent local colorectal tumor recurrence following surgical resection. Colorectal cancers are the third largest cancer killer in the US with the identificationof an estimated new 40,000 rectal and 103,000 colon cancer cases in 2010. Surgical resection is the standard of care for curative treatment, but tumor recurrence remains a significant threat to survival, occurring in an estimated 27% of all patients. The 5-year incidence of locoregional recurrence for those colon cancer patients who receive 'curative' surgery is nearly 12%, and has been estimated to be more than double for rectal cancer patients. About half of local colorectal recurrences occur directly at the anastamosis or resected tumor bed. More than 50% of patients do not have metastasis at the time of local recurrence, highlighting the potential survival benefit of local tumor control. The utilization of adjuvant chemotherapy is limited by high systemic toxicities and poor localization to the site of disease. Our non-woven fiber mesh design shares properties found in conventional commercially-available surgical mesh materials with the significant benefit of prolonged drug delivery which can be tuned with a high level of control by 'doping'/blending with our proprietary copolymer. In this proposal, we will optimize our tunable mesh to the following design criteria: 1) prolonged drug release kinetics with multiple cell cycle duration, 2) elimination of burst release kinetics to guard against acute toxicity, 3) maintenance of stable lactone form of camptothecin drug, 4) full biodegradation over 3-6 months to avoid a chronic foreign body response, and 5) demonstration of long-term anti-cancer efficacy in vitro. The two Specific Aims of this proposal are: 1) optimize electrospinning manufacturing parameters for candidate polymer blend compositions and characterize resultant biodegradable non-woven fiber meshes, and 2) characterize dose-dependent release kinetics of SN38 chemotherapy-loaded meshes and evaluate in vitro anti-cancer efficacy. At the completion of these aims, we will have a prototype chemotherapy-eluting mesh with prolonged non-burst drug release that biodegrades in < 6 months. Our drug-eluting mesh will be affixed to the tissue adjacent to the resection margins and anastamosis at the time of surgery using standard GIA surgical staplers, thus not requiring significant changes to standard of care drugs, procedures, or instruments. Our product will minimize the side effects associated with intravenously-administered chemotherapy and will reduce the locoregional recurrence rate of residual malignant disease while preserving bowel function with the goal of increased survival and patient quality of life.